Autologous Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus (ASSIST)

Systemic Lupus Erythematosus Clinical Trial

— ASSIST  

Official title:

An Open-Label, Phase II Multicenter Cohort Study of Immunoablation With Cyclophosphamide and Antithymocyte-Globulin and Transplantation of Autologous Cd34-Enriched Hemapoietic Stem Cells Versus Currently Available Immunosuppressive/Immunomodulatory Therapy for Treatment of Refractory Systemic Lupus Erythematosus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00750971
• Other study ID #: CT-1306
• Status: Recruiting
• Phase: Phase 2
• First received: September 10, 2008
• Last updated: March 17, 2017
• Start date: August 2008
• Est. completion date: August 2020

Study information

• Verified date: March 2017
• Source: Charite University, Berlin, Germany
• Contact: Falk Hiepe, Prof.
• Phone: +49 30 450 513026
• Email: falk.hiepe[@]charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

While glucocorticoids and immunosuppressants ameliorate manifestations of SLE in many patients, current therapies are insufficient to control the disease in a subset of patients, and their clinical prognosis remains poor due to the development of vital organ failure, cumulative drug toxicity and to the increased risk of cardiovascular disease and malignancy. Immunoablative chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) has recently emerged as a promising experimental therapy for severely affected patients, providing them the potential to achieve treatment-free, long-term remission. The investigators postulate that immunoablative therapy eliminates or effectively reduces the level of autoreactive T and B lymphocytes and then regeneration of de novo immunity resets the autoreactive immune system into a self-tolerant, protective immune system resulting in prolonged and treatment-free remission.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of SLE according to American College of Rheumatology (ACR) classification criteria

2. Age between 18 and 60 years, inclusive

3. Provision of informed consent

4. Active disease, refractory to standard immunosuppressive therapy defined as:

• BILAG level A and a SLEDAI-score of at least 10, despite treatment with high-dose corticosteroids and pulse intravenous CYC at doses of 500-1000mg/m2 for at least 6 months or mycophenolate mofetil (MMF) at doses of at least 2g -

• Lupus nephritis with renal biopsy performed within one year prior to screening showing glomerulonephritis WHO class III or IV

• Parenchymal disease of heart or lung

• Neuropsychiatric lupus

• Autoimmune cytopenia OR

• recurrence of disease activity (defined as BILAG level A and a SLEDAI of at least 10) within one year after successful induction therapy with cyclophosphamide or MMF in the presence of an adequate maintenance therapy with either cyclophosphamide (at least 500mg/m2 monthly), mycophenolate mofetil (at least 2g daily), azathioprine (at least 1.5mg/kg/d), methotrexate (at least 15mg weekly), cyclosporine (at least 3mg/kg/d) in patients with persistent anti-dsDNA antibodies

Exclusion Criteria:

1. Severe concomitant disease or organ damage

• renal: renal insufficiency with glomerular filtration rate below 40ml/min

• cardiac: congestive heart failure, LVEF < 40% determined by echocardiogram, uncontrolled arrhythmia

• pulmonary: mean pulmonary arterial pressure >50mmHg, DLCO < 40 % predicted

• gastrointestinal: liver cirrhosis; SGOT, SGPT greater than 2 x the upper limit of normal, unless due to active lupus

2. Ongoing cancer or history of malignancy within 5 years of screening

3. Women who are pregnant or breastfeeding or use non-reliable methods of contraception

4. Subjects with active systemic infection

5. Subjects with history of active viral infection within 6 months prior to screening, known HIV-infection or chronic Hepatitis B or Hepatitis C

6. History of allergic reaction to cyclophosphamide, G-CSF or ATG

7. Use of immunosuppressive agents for indications other than SLE

8. Any comorbidity that in the opinion of the investigator would jeopardize the ability of the subject to tolerate therapy

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Procedure:
• Immunoablation and Autologous Hematopoietic Stem Cell Transplantation
Transplantation of purified CD34+ autologous hematopoietic stem cells mobilized with cyclophosphamide (200mg/m2)and G-CSF (10µg/kg/d) after immunoablation with cyclophosphamide (200mg/kg)and rabbit-antithymocyteglobulin (90mg/kg)

Locations

Country	Name	City	State
Germany	Universitätsmedizin Charité	Berlin
Germany	Universitätsklinik Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinik Heidelberg	Heidelberg
Germany	Universitätsklinik Köln	Köln
Germany	Universitäsklinik Mainz	Mainz
Germany	Universitätsklinik Tübingen	Tübingen
Germany	Universitätsklinik Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (4)

Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S, Mei H, Radtke H, Gromnica-Ihle E, Burmester GR, Arnold R, Radbruch A, Hiepe F. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood. 2009 Jan 1;113(1):214-23. doi: 10.1182/blood-2008-07-168286. — View Citation

Jayne D, Passweg J, Marmont A, Farge D, Zhao X, Arnold R, Hiepe F, Lisukov I, Musso M, Ou-Yang J, Marsh J, Wulffraat N, Besalduch J, Bingham SJ, Emery P, Brune M, Fassas A, Faulkner L, Ferster A, Fiehn C, Fouillard L, Geromin A, Greinix H, Rabusin M, Saccardi R, Schneider P, Zintl F, Gratwohl A, Tyndall A; European Group for Blood and Marrow Transplantation.; European League Against Rheumatism Registry.. Autologous stem cell transplantation for systemic lupus erythematosus. Lupus. 2004;13(3):168-76. — View Citation

Rosen O, Thiel A, Massenkeil G, Hiepe F, Häupl T, Radtke H, Burmester GR, Gromnica-Ihle E, Radbruch A, Arnold R. Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells. Arthritis Res. 2000;2(4):327-36. — View Citation

Thiel A, Alexander T, Schmidt CA, Przybylski GK, Kimmig S, Kohler S, Radtke H, Gromnica-Ihle E, Massenkeil G, Radbruch A, Arnold R, Hiepe F. Direct assessment of thymic reactivation after autologous stem cell transplantation. Acta Haematol. 2008;119(1):22-7. doi: 10.1159/000117824. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SLEDAI		48 months
Secondary	Serologic response (autoantibodies)		48 months
Secondary	Immune Reconstitution		48 months
Secondary	Organ-specific response parameters		48 months